The overall goal of this proposal is (1) to develop selective anti- human immunodeficiency virus (HIV) agents by taking advantage of unique properties of HIV pol gene products, reverse transcriptase (RT), protease and endonuclease (EN), (2) to study the metabolism and mechanism of action of antiviral agents, (3) to study the mechanism and development of drug resistance in order to get insight into using those agents effectively. The specific aims include: a) the study of biochemical events in cells infected with HIV, b) a comparison of virus specified and human enzymes, c) designing and synthesizing compounds which could interact with the virus specified enzymes, and d) study of those compounds which have potential anti-HIV activity with respect to their biological activity, metabolism and mechanism of action. Some of these projects will be done in collaboration with other investigators involved with this proposed program, but the study of RT as one of the potential enzyme targets and the study of the biochemical pharmacology of potential anti-HIV drugs are the major focus of this laboratory.